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Optimizing individual nutrition in preterm very low birth weight infants: double-blinded randomized controlled trial

Journal of Perinatology volume 40, pages 655–665 (2020)Cite this article

Subjects

Abstract

Objective

In preterm neonates fed human milk, fortification may be adjusted by (1) optimization, based on growth rate and serum nutrient analyses, or (2) individualization, based on serial milk nutrient analyses. The primary aim was to determine whether individualized plus optimized nutrition (experimental) improves velocity of weight gain and linear growth from birth to endpoint (36 weeks postmenstrual age or discharge) when compared with optimized nutrition alone (controls).

Study design

Double-blinded parallel group randomized trial in 120 neonates <29 weeks gestational age (GA) or <35 weeks and small for GA (birth weight < 10th centile).

Result

Weight-gain velocity (13.1 ± 2.1, n = 57 controls, vs. 13.0 ± 2.6 g kg−1 day−1, n = 59 experimental, P = 0.87), linear growth (0.9 ± 0.2, n = 55, vs. 0.9 ± 0.2 cm week−1, n = 52, P = 0.90) and frequency of weight/length disproportion (2% vs. 2%, P = 0.98) were similar in both groups.

Conclusions

Individualized plus optimized nutrition does not improve weight gain, linear growth, or weight/length disproportion at endpoint versus optimized nutrition alone.

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Acknowledgements

This study was funded by the Gerber Foundation ($300,000) and in part by the CCRAC Award from the Children’s Foundation ($100,000). Cost of breast milk analyses included $58,000 for the equipment (purchase and 3-year maintenance and supplies) and $201,000 for salaries and fringes for 0.5 FTE of a dietitian 0.33 FTE for a formula technician. Jülide Sisman, MD, MS and LSB, MS, conducted blinded meetings of the data safety committee every 6 months to review safety, adverse events, and futility. Susan Chacko, RN, Maria DeLeon, and RN were research coordinators for part of this study. Chen Du, RD, Elizabeth Brammer, RD and Audrey Edwards, RD, dietitians at Parkland Hospital, obtained anthropometric measurements for this study and participated in patient recruitment, assessments of growth and laboratory results and recommendations for nutritional interventions. Christopher Clark, IT specialist at Parkland Hospital, extracted data from EPIC at Parkland. LaShunda Wilson, Kennissia Collins, and Brandon Hadnot (formula technicians at Parkland Hospital) measured human milk samples in both groups and supplemented milk in the experimental group. Blair Holbein, PhD, DCS helped with IRB approval of the NIRS measurements. Dr Holbein is supported by NCATS “National Center for Advancing Translational Sciences of the NIH” UL1TR001105.

Preliminary results were submitted in abstract form:

• LPB, CRR, RH, LSB, CSL, and MC. Optimizing individual nutrition in preterm infants: randomized clinical trial (RCT). This abstract was presented at the Pediatric Academy Societies Meeting at Baltimore, MD, 4/29/19.

• LPB, CRR, RH, LSB, CSL, EP, TJ, MC, and PJB. Double-blinded randomized controlled trial (RCT) of Optimizing Individual Nutrition in Preterm (PT) very low birth weight infants: analysis of nutrient intake and growth patterns. Submitted for presentation at PAS, Philadelphia, PA, May 2020.

Funding

This study was supported by a National Grant from the Gerber Foundation (LPB), the George L. MacGregor Professorship (CRR) and the following grant: Children’s Medical Center Clinical Advisory Committee (CCRAC)—Senior Investigator Research Award—New Direction (LPB, 2015−17). The funding organizations had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review and approval of the manuscript, and decision to submit the manuscript for publication.

Author contributions

LPB conceptualized and designed the study, developed the protocol and the database, collected and reviewed data from the medical records, participated in the interpretation of the data, wrote the first draft of the manuscript, critically reviewed the revisions, and approved the final manuscript as submitted. CRR and RH conceptualized and designed the study. Each participated in the interpretation of the data, critically reviewed the revisions, and approved the final manuscript as submitted. LSB, MS, conceptualized and designed the study. He developed and ran the randomization algorithm and prepared three sets (one per stratum) of sequential cards with unique trial number. He merged into a single spreadsheet the randomized allocation data with data extracted from the medical records, conducted statistical analyses, prepared the CONSORT flow diagram, participated in the interpretation of the data, critically reviewed the revisions, and approved the final manuscript as submitted. CSL obtained anthropometric measurements for this study and participated in patient recruitment, assessments of growth and laboratory results, and nutritional interventions. She participated in the interpretation of the data, critically reviewed the revisions, and approved the final manuscript as submitted. EP participated in the organization of the trial, development of the methods and training of the personnel who ran the milk analyses. She organized and supervised patient allocation and milk analyses, supplementation, and documentation in a separate room, the infant nutrition center. She had no role in patient enrollment or patient care. She participated in the interpretation of the data, critically reviewed the revisions, and approved the final manuscript as submitted. TJ obtained anthropometric measurements for this study and participated in patient recruitment, assessments of growth and laboratory results, and nutritional interventions. She participated in the interpretation of the data, critically reviewed the revisions, and approved the final manuscript as submitted. MC was research coordinator for a large part of this study. She recruited and measured patients in the NICU and at follow-up. She extracted data from medical records into databases, critically reviewed the manuscript, and approved the final manuscript as submitted. PJB collected data on all infants, participated in the interpretation of the data, critically reviewed the revisions, and approved the final manuscript as submitted.

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Authors and Affiliations

  1. Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of Texas, Southwestern Medical Center, Dallas, TX, USA

    Luc P. Brion, Charles R. Rosenfeld, Roy Heyne, Maria Caraig & Patti J. Burchfield

  2. Parkland Health & Hospital System, Dallas, TX, USA

    L. Steven Brown, Cheryl S. Lair, Elen Petrosyan & Theresa Jacob

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  1. Luc P. Brion
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Correspondence to Luc P. Brion.

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Brion, L.P., Rosenfeld, C.R., Heyne, R. et al. Optimizing individual nutrition in preterm very low birth weight infants: double-blinded randomized controlled trial. J Perinatol 40, 655–665 (2020). https://doi.org/10.1038/s41372-020-0609-1

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